Version July 2025
Myelosuppression: Thiotepa may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. Hematopoietic progenitor (stem) cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression after high doses of thiotepa.
Carcinogenicity: Thiotepa should be considered potentially carcinogenic in humans.
Note: Dosing and frequency may vary by protocol; refer to individual protocols. In pediatric patients, dosing may be based on either BSA (mg/m2) or weight (mg/kg); use extra precaution to verify dosing parameters during dosage calculations.
Antiemetics may be recommended for prevention of nausea and vomiting. In pediatric patients, doses ≥300 mg/m2 are associated with a high emetic potential and doses <300 mg/m2 are associated with a low emetic potential (Ref).
CNS malignancy, newly diagnosed, high-dose chemotherapy followed by autologous stem cell rescue (ASCR), consolidation: Infants ≥6 months and Children <3 years: IV: 10 mg/kg/dose daily for 2 days on days 0 and 1 in combination with carboplatin, followed by ASCR (Ref).
CNS malignancy, recurrent or refractory followed by autologous stem cell rescue (ASCR):
Infants and Children ≤25 kg: IV: 6.67 mg/kg/dose daily for 3 days followed by ASCR approximately 72 hours after the third dose. A second cycle of thiotepa/ASCR was administered at least 28 days after completion of first course if sufficient hematologic recovery and no tumor progression (Ref).
Children and Adolescents >25 kg: IV: 200 mg/m2/dose daily for 3 days followed by ASCR approximately 72 hours after the third dose. A second cycle of thiotepa/ASCR was administered at least 28 days after completion of first course if sufficient hematologic recovery and no tumor progression (Ref).
Hematopoietic stem cell transplant (HSCT), autologous, conditioning regimen: Infants, Children, and Adolescents: IV: 300 mg/m2/dose daily for 3 days beginning 8 days prior to transplant OR 300 mg/m2/dose daily for 3 days beginning 5 days prior to transplant in combination with other preconditioning therapies (protocols vary). For infants, some protocols report using a dose of 10 mg/kg/dose daily for 3 days (Ref).
Hematopoietic stem cell transplant (HSCT) for acute leukemias; allogeneic, conditioning regimens:
Treosulfan/fludarabine/thiotepa regimen: Infants, Children, and Adolescents: IV: 5 mg/kg/dose daily for 2 days starting on day −2 in combination with treosulfan and fludarabine (Ref).
TBI-Thio-Cy regimen: Children and Adolescents: IV: 5 mg/kg/dose for 2 doses over 1 or 2 days beginning either 7 or 4 days prior to transplant depending on protocol in combination with total body irradiation and cyclophosphamide (Ref).
Clo-Mel-Thio: Children and Adolescents: IV: 10 mg/kg/dose daily for 1 day beginning 4 days prior to transplant in combination with clofarabine and melphalan; patients were receiving second or third HSCT (Ref).
Hematopoietic stem cell transplant (HSCT) for beta-thalassemia, class 3; allogeneic conditioning: Infants, Children, and Adolescents: Tepadina: IV: 5 mg/kg/dose every 12 hours for 2 doses 6 days prior to HSCT in combination with high-dose busulfan and cyclophosphamide (Ref).
Hematopoietic stem cell transplant (HSCT) for neuroblastoma; autologous, conditioning regimen:
Single transplant: Children and Adolescents: IV: 300 mg/m2/dose daily for 3 days for a total dose of 900 mg/m2 beginning 8 days prior to transplant (day −8, −7, −6) in combination with carboplatin and topotecan (Ref).
Tandem transplant:
Infants and Children ≤12 kg: IV: 10 mg/kg/dose daily for 3 days beginning 7 days before the first transplant and followed by cyclophosphamide (Ref).
Children >12 kg and Adolescents: IV: 300 mg/m2/dose daily for 3 days beginning 7 days before the first transplant and followed by cyclophosphamide (Ref).
Hematopoietic stem cell transplant (HSCT) for nonmalignant hematologic disorders, allogeneic, conditioning regimens: Infants, Children, and Adolescents: IV: 10 mg/kg/dose as a single dose in a fludarabine-based combination regimen (Ref).
Leukemia, relapsed or refractory:
TVTC regimen:
Infants: IV: 0.5 mg/kg/dose over 4 hours on day 2 of a 28-day regimen in combination with topotecan, clofarabine, and vinorelbine; in the trial, the youngest patient was 8 months of age (Ref).
Children and Adolescents: IV: 15 mg/m2/dose over 4 hours on day 2 of a 28-day regimen in combination with topotecan, clofarabine, vinorelbine (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients. Refer to specific protocol for management in pediatric patients if available.
Adult:
Central nervous system toxicity, severe or life-threatening: Discontinue thiotepa and provide supportive care.
Hypersensitivity reactions (eg, anaphylaxis or other clinically significant reaction): Discontinue thiotepa and manage as appropriate; monitor until signs/symptoms resolve.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; reduced dose may be warranted. Use may be contraindicated with existing renal impairment and should be limited to cases where benefit outweighs risk.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; reduced dose may be warranted. Use may be contraindicated with existing hepatic impairment and should be limited to cases where benefit outweighs risk.
(For additional information see "Thiotepa: Drug information")
Dosage guidance:
Clinical considerations: Antiemetics are recommended to prevent nausea and vomiting; thiotepa (IV) is associated with a moderate emetic potential (Ref).
Hematopoietic cell transplant conditioning regimen for CNS malignancy (off-label use):
Single agent therapy: IV: 150 mg/m2/dose every 12 hours for 6 doses, followed by cell reinfusion 96 hours after completion of thiotepa (Ref).
Thiotepa/Busulfan/Cyclophosphamide (TBC regimen): IV: 250 mg/m2/day for 3 days beginning 9 days prior to autologous transplant (in combination with busulfan and cyclophosphamide) (Ref).
Thiotepa/Carmustine regimen (TT-BCNU regimen): IV: 5 mg/kg/day for 2 days (total dose: 10 mg/kg) beginning 5 days prior to autologous transplant (in combination with carmustine) (Ref) or 5 mg/kg every 12 hours for 2 days (total dose: 20 mg/kg) beginning 5 days prior to autologous transplant (in combination with carmustine) (Ref).
Leptomeningeal metastases (off-label use/route): Intrathecal: 10 mg twice a week (on days 1 and 4 each week) for 8 weeks (Ref).
Primary CNS lymphoma, newly diagnosed, induction therapy (off-label use): Medically fit adults ≤70 years of age: IV: 30 mg/m2 on day 4 every 3 weeks (in combination with methotrexate, cytarabine, and rituximab; MATRix regimen) for 2 to 4 cycles; patients in complete remission, partial remission, or stable disease after 2 induction cycles received an additional 2 induction cycles, and then (if responded or stable) proceeded to either whole-brain radiation therapy or autologous cell transplantation (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; decreased renal excretion may result in increased thiotepa and TEPA plasma concentrations and increased toxicity. Monitor patients with moderate (CrCl 30 to 59 mL/minute) to severe (CrCl <30 mL/minute) impairment for toxicity.
Hemodialysis: Thiotepa is dialyzable.
Hepatic impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; thiotepa is extensively hepatically metabolized. Moderate (bilirubin >1.5 to 3 times ULN and any AST) or severe (bilirubin >3 times ULN and any AST) impairment may result in increased plasma concentrations and increased toxicity. Monitor closely for toxicity.
Hepatotoxicity during treatment: Hepatic sinusoidal obstruction syndrome (SOS, also called veno-occlusive disease [VOD]): Provide supportive care if SOS develops.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
As a preparative regimen prior to allogeneic or autologous hematopoietic progenitor cell transplantation:
Frequency not defined:
Central nervous system: Intracranial hemorrhage, seizure
Dermatologic: Skin rash
Gastrointestinal: Mucositis
Hematologic & oncologic: Anemia, hemorrhage, neutropenia, thrombocytopenia
Hepatic: Increased serum ALT, increased serum AST, increased serum bilirubin
Infection: Cytomegalovirus disease
Respiratory: Pneumonia
Other approved/nonapproved uses:
Frequency not defined:
Dermatologic: Alopecia, contact dermatitis, dermatitis, skin depigmentation, skin rash, urticaria
Central nervous system: Dizziness, fatigue, headache
Endocrine & metabolic: Amenorrhea
Gastrointestinal: Abdominal pain, anorexia, nausea, vomiting
Genitourinary: Cystitis, dysuria, hemorrhagic cystitis, inhibition of Spermatogenesis, urinary retention
Hypersensitivity: Anaphylactic shock, hypersensitivity reaction
Infection: Infection
Local: Pain at injection site
Neuromuscular & skeletal: Weakness
Ophthalmic: Blurred vision, conjunctivitis
Respiratory: Asthma, laryngeal edema, wheezing
Miscellaneous: Febrile reaction
<1%, postmarketing, and/or case reports: Abnormal gait, acute myelocytic leukemia, acute respiratory distress, acute sinusitis, amnesia, apathy, aphasia, arteriosclerosis (pulmonary arteriopathy), ascites, aspiration, ataxia, behavioral problems, blepharoptosis, blindness, blood coagulation disorder, blood platelet disorder (refractoriness to transfusion), bone marrow aplasia, bone marrow depression (bone marrow transplant rejection), bradycardia, brain disease, candidiasis, capillary leak syndrome, cardiac failure, cerebrovascular accident, cognitive dysfunction, coma, confusion, cranial nerve palsy, deafness, delirium, depression, diarrhea, disorientation, drowsiness, dysphagia, dyspnea on exertion, encephalitis, enterocolitis, epstein-barr infection, fever, forgetfulness, fungal infection, gastritis, gastroenteritis, gastrointestinal hemorrhage, hallucination, hematuria, hemiplegia, hepatomegaly, hyponatremia, hypotonia, immunosuppression, infection due to enterococcus, interstitial pulmonary disease, klebsiella species, lesion (including central nervous system and white matter), leukemia (recurrent), leukoencephalopathy, lower respiratory tract infection (viral), lymphoproliferative disorder (posttransplant), malaise, malignant lymphoma (including central nervous system lymphoma), malignant neoplasm (recurrence), malignant neoplasm of breast (metastatic), memory impairment, motor dysfunction, mouth disease (palatal disorder), myelodysplastic syndrome, neoplasm (metastatic), neurotoxicity, pain, papilledema, paralysis (retrobulbar), paresis (quadriparesis), pericardial effusion, pericarditis, pneumonitis, pseudomonas infection, psychomotor retardation, pulmonary aspergillosis, pulmonary disease, pulmonary hypertension, pulmonary veno-occlusive disease, pure red cell aplasia, renal failure, respiratory distress, respiratory tract infection, sepsis, septic shock, speech disturbance, staphylococcal bacteremia, staphylococcal infection, Stevens-Johnson Syndrome, strabismus, subarachnoid hemorrhage, subdural hematoma, suicidal ideation, thrombotic thrombocytopenic purpura (cerebral), toxic epidermal necrolysis, toxic nephrosis, tremor, urinary tract infection, vasodilation (cerebral ventricle), ventricular hypertrophy, weight gain
Known hypersensitivity (allergy) to thiotepa or any component of the formulation; concomitant use with live or attenuated vaccines (Tepadina).
Canadian labeling: Additional contraindications (not in the US labeling): Pregnancy; breastfeeding.
Concerns related to adverse effects:
• Bone marrow suppression: Myelosuppression (leukopenia, thrombocytopenia, and anemia) may commonly occur, particularly when used as part of the preparative regimen for hematopoietic cell transplantation (HCT) or in patients with compromised bone marrow function. For allogeneic transplant, do not initiate the HCT conditioning regimen if a donor is not available. Infection or bleeding may occur; death due to septicemia and hemorrhage has occurred. Myelosuppression (including fatal cases) has also been reported with intravesicular administration (due to systemic absorption).
• CNS effects: Fatal encephalopathy has been reported in patients receiving high-dose thiotepa. Headache, apathy, psychomotor retardation, disorientation, confusion, amnesia, hallucinations, drowsiness, somnolence, seizures, coma, inappropriate behavior, and forgetfulness have also been reported (may be dose dependent). CNS toxicity, including seizures and intracranial hemorrhage was reported in pediatric patients who receive the recommended dose in combination with busulfan and cyclophosphamide as a conditioning regimen for beta thalassemia; do not exceed the recommended dose.
• Dermatologic toxicity: In patients receiving high-dose thiotepa, the parent drug and/or its active metabolites may be partially excreted through the skin. Thiotepa may cause skin discoloration, pruritus, blistering, desquamation, and peeling (may be more severe in skin folds, groin, axillae, and neck areas, and under dressings). Change occlusive dressing and clean covered skin at least twice daily during and for 48 hours after thiotepa administration (when used as a component of the HCT preparative regimen). Patients should shower/bathe in water at least twice daily through 48 hours after receiving thiotepa. Change bed sheets daily. Avoid topical creams/ointments during thiotepa therapy as to not impede excretion (Van Schandevy 2019). Accidental thiotepa exposure is also associated with skin reactions; wash skin thoroughly with soap and water and flush mucous membranes if skin and/or mucous membrane contact occurs.
• Hepatic sinusoidal obstruction syndrome: Hepatic sinusoidal obstruction syndrome (SOS, also called veno-occlusive disease [VOD]) may occur in patients receiving thiotepa in combination with busulfan and cyclophosphamide as a preparative regimen prior to HCT.
• Hypersensitivity: Clinically significant hypersensitivity reactions (including anaphylaxis) have occurred.
• Secondary malignancies: Thiotepa is potentially carcinogenic; myelodysplastic syndrome and acute myeloid leukemia (AML) have been reported. There is an increased risk of secondary malignancies with thiotepa use.
Concurrent drug therapy issues:
• Vaccines: Do not administer live or attenuated viral or bacterial vaccines until the immunosuppressive effects of thiotepa have resolved.
Other warnings/precautions:
• Intrathecal safety: When used for intrathecal administration (off-label route), should not be prepared during the preparation of any other agents. After preparation, keep intrathecal medications in an isolated location or container clearly marked with a label identifying as "intrathecal" use only. Delivery of intrathecal medications to the patient should only be with other medications also intended for administration into the central nervous system (ASCO/ONS [Neuss 2016]).
Tepylute: FDA approved June 2024; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Tepylute is available as a 10 mg/mL solution for intravenous use after dilution. Consult the prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Tepylute: 15 mg/1.5 mL (1.5 mL); 100 mg/10 mL (10 mL) [contains polyethylene glycol (macrogol)]
Solution Reconstituted, Injection:
Generic: 15 mg (1 ea); 100 mg (1 ea)
Solution Reconstituted, Injection [preservative free]:
Tepadina: 15 mg (1 ea); 100 mg (1 ea)
Generic: 15 mg (1 ea); 100 mg (1 ea)
Yes
Solution (reconstituted) (Tepadina Injection)
15 mg (per each): $360.00
100 mg (per each): $2,160.00
Solution (reconstituted) (Thiotepa Injection)
15 mg (per each): $240.00 - $965.00
100 mg (per each): $2,160.00 - $5,125.00
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Tepadina: 15 mg (1 ea); 100 mg (1 ea)
Generic: 15 mg (1 ea); 100 mg (1 ea)
In children, thiotepa is associated with a high emetic potential at doses ≥300 mg/m2; antiemetics are recommended to prevent nausea and vomiting (Ref). Ensure increased showers/baths conducted during therapy if applicable (see "Warnings/Precautions").
Parenteral: IV: Must be diluted prior to administration; high doses (pediatric) are administered as an IV infusion (eg, over 2- to 4-hour infusion). Infusion times may vary by protocol; refer to specific protocols. For Tepadina (and associated generic products), administer using a 0.2 micron in-line filter; flush line prior to and after infusion with ~5 mL NS.
Antiemetics may be recommended to prevent nausea and vomiting; thiotepa (IV) is associated with a moderate emetic potential in adults (Ref).
IV: Administer over 3 hours via a central line (when administering as part of the preparative regimen for hematopoietic cell transplantation in class 3 beta-thalassemia). Infusion times may vary by protocol or dose for off-label uses; refer to specific protocols. Filtering does not alter thiotepa potency. Tepadina: Administer using a 0.2 micron in-line filter; flush line prior to and after infusion with ~5 mL NS.
Intrathecal route (off-label use/route): Was administered in 10 mL (preservative free) buffered solutions (Ref).
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Tepadina: Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light; do not freeze. Reconstituted solution (10 mg/mL) is stable for 8 hours when stored at 2°C to 8°C (36°F to 46°F). Solution further diluted for infusion in NS is stable for 24 hours when stored at 2°C to 8°C (36°F to 46°F), or for 4 hours when stored at 25°C (77°F).
Generic product labeling: Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light. Reconstituted solutions (10 mg/mL) are stable for up to 8 hours when stored under refrigeration. Solutions further diluted for infusion in NS should be used immediately.
Intrathecal thiotepa (off-label use/route): After preparation, keep intrathecal medications in an isolated location or container clearly marked with a label identifying as "intrathecal" use only.
To reduce the risk of graft rejection when used in conjunction with high-dose busulfan and cyclophosphamide as a preparative regimen for allogeneic hematopoietic progenitor (stem) cell transplantation in patients with class 3 beta-thalassemia (Tepadina: FDA approved in pediatric patients ≥1 month of age); treatment of superficial tumors of the bladder (FDA approved in adults); palliative treatment of adenocarcinoma of breast or ovary (FDA approved in adults); control of pleural, pericardial, or peritoneal effusions caused by metastatic tumors (FDA approved in adults); has also been used as part of a conditioning regimen prior to autologous or allogeneic hematopoietic stem cell transplantation.
Note: Although included in the manufacturer's labeling as approved uses in adults, other contemporary therapies have replaced the use of thiotepa for the treatment of papillary bladder, ovarian, and breast cancers, as well as for malignant intracavitary effusions.
Thiotepa may be confused with thioguanine
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral; epidural and intrathecal medications) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Intrathecal medication safety: The American Society of Clinical Oncology (ASCO)/Oncology Nursing Society (ONS) chemotherapy administration safety standards (ASCO/ONS [Neuss 2016]) encourage the following safety measures for intrathecal chemotherapy:
• Intrathecal medication should not be prepared during the preparation of any other agents
• After preparation, keep in an isolated location or container clearly marked with a label identifying as "intrathecal" use only
• Delivery to the patient should only be with other medications also intended for administration into the central nervous system
Substrate of CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CycloPHOSphamide: Thiotepa may decrease active metabolite exposure of CycloPHOSphamide. More specifically, thiotepa may decrease the rate of cyclophosphamide conversion to its primary active metabolite, 4-hydroxycyclophosphamide. Risk C: Monitor
CYP2B6 Substrates (High risk with Inhibitors): Thiotepa may increase serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor
CYP3A4 Inducers (Moderate): May increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Moderate) may decrease serum concentration of Thiotepa. Risk C: Monitor
CYP3A4 Inducers (Strong): May increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Strong) may decrease serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inducers. If concomitant use is unavoidable, monitor for adverse effects. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Thiotepa. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Thiotepa. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May decrease active metabolite exposure of Thiotepa. CYP3A4 Inhibitors (Strong) may increase serum concentration of Thiotepa. Management: Avoid coadministration of thiotepa and strong CYP3A4 inhibitors. If concomitant use cannot be avoided, monitor for thiotepa adverse effects and decreased efficacy. Risk D: Consider Therapy Modification
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Thiotepa may decrease therapeutic effects of Vaccines (Live). Thiotepa may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to therapy initiation in patients who could become pregnant. Effective contraception should be used during treatment and for at least 6 months after the final dose. Patients with partners who could become pregnant should use effective contraception during therapy and for at least 1 year after the final dose.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to thiotepa may cause fetal harm.
CBC with differential and platelet count (baseline, frequently throughout therapy), uric acid, urinalysis, renal and hepatic function tests. Evaluate pregnancy status prior to treatment. Monitor for signs/symptoms of hypersensitivity reactions, dermatologic toxicity, hepatic sinusoidal obstruction syndrome, and CNS toxicity.
Thiotepa is an alkylating agent which produces cross-linking of DNA strands leading to inhibition of DNA, RNA, and protein synthesis; thiotepa is cell-cycle independent (Perry 2012)
Distribution: Vdss: 0.3 to 1.6 L/kg; penetrates into CSF (Maanen 2000); the mean volume of distribution following a single IV dose in pediatric patients receiving a 5 mg/kg dose was 1.2 L/kg or 30 L/m2.
Protein binding: ~10% to 20%.
Metabolism: Extensively hepatic via cytochrome P450 system, primarily to the major (active) metabolite TEPA (Maanen 2000; Perry 2012).
Half-life elimination: Terminal:
Pediatrics (5 mg/kg IV dose): Thiotepa: 1.7 hours; TEPA: 4 hours.
Adults (20 mg to 250 mg/m2 IV dose): Thiotepa: 1.4 to 3.7 hours; TEPA: 4.9 to 17.6 hours.
Excretion: Urine (<2% of thiotepa dose; <11% of TEPA); dermal via sweat (Horn 1989).
Altered kidney function: Thiotepa and TEPA exposure increased 1.5-fold and 2.6-fold, respectively, following administration of multiple doses of 120 mg/m2/day in a patient with moderate renal impairment (CrCl 38 mL/minute), compared to patients with normal renal function.
Hepatic function impairment: In two adult patients with liver metastases and moderate hepatic impairment receiving multiple thiotepa doses of 7 mg/kg (administered every 2 days with cyclophosphamide), thiotepa exposure increased by 1.6-fold and 1.8-fold compared to a patient with normal hepatic function.
